Stress response as implemented by hibernating ribosomes: a structural overview

Abstract

Protein synthesis is one of the most energy demanding cellular processes. The ability to regulate protein synthesis is essential for cells under normal as well as stress conditions, such as nutrient deficiencies. One mechanism for protein synthesis suppression is the dimerization of ribosomes into hibernation complexes. In most cells, this process is promoted by the hibernating promoting factor (HPF) and in a small group of Gram‐negative bacteria (γ‐proteobacteria), the dimer formation is induced by a shorter version of HPF (HPFshort) and by an additional protein, the ribosome modulation factor. In most bacteria, the product of this process is the 100S ribosome complex. Recent advances in cryogenic electron microscopy methods resulted in an abundance of detailed structures of near atomic resolutions 100S complexes that allow for a better understanding of the dimerization process and the way it inhibits protein synthesis. As ribosomal dimerization is vital for cell survival, this process is an attractive target for the development of novel antimicrobial substances that might inhibit or stabilize the complex formation. As different dimerization processes exist among bacteria, including pathogens, this process may provide the basis for species‐specific design of antimicrobial agents. Here, we review in detail the various dimerization mechanisms and discuss how they affect the overall dimer structures of the bacterial ribosomes.

The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus

“…S. aureus HPF is one of the predominant proteins induced upon host cell internalization and during infections (13,14). For reviews of the topic, see references (15)(16)(17)(18)(19).…”

Physiology of guanosine-based second messenger signaling in Bacillus subtilis

“…Nutrient deprivation, stress conditions or stationary phase conditions is often accompanied by the formation of 100S ribosomal particles, which are dimers of 70S ribosomes (Gohara and Yap 2018;Matzov et al 2019;Prossliner et al 2018). Formation of B. subtilis 100S ribosome dimers is mediated by the hibernation-promoting factor (HPF) protein YvyD, which is upregulated under stress conditions in a (p)ppGpp-dependent manner (Eymann et al 2002;Schafer et al 2020).…”

Coordinated Regulation of Rsd and RMF for Simultaneous Hibernation of Transcription Apparatus and Translation Machinery in Stationary-Phase Escherichia coli

“…In the case of the bacterial group having long HPF, several structures have been proposed for the ribosome dimer (For instance, Matzov et al, 2019). Accordingly, the 70S–70S interface within ribosome dimers appeared different from that of E. coli (Kato et al, 2010; Beckert et al, 2018).…”